This research involves the study of stereoselective pharmacological effects of ICRF-159 analogues in order to provide leads for maximizing the therapeutic efficacy of bisdioxopiperazines relative to their potential use as antimetastatic drugs or modifiers of anthracycline-induced toxicity. For antimetastatic activity, geometrical isomers will be investigated for their effect on growth and metastasis in the allogeneic hamster lung adenocarcinoma model as well as the syngeneic Bl6 melanoma and Lewis lung tumor models employing C57BL/6 mice. In addition to a direct effect on the tumor cells, a concomitant effect on the immunological competency of the host will be determined. The effect of analogue pretreatment on acute anthracycline-induced toxicity in the isolated blood-perfused dog heart, anthracycline-induced lethality in Syrian golden hamsters and anthracycline-induced tissue alterations will be examined. Studies are designed to provide leads for new anticancer drug development.